Project Summary/Abstract Background: Approximately 395,000 people suffer out-of-hospital cardiac arrest (OHCA) each year in the US. The survival rate is <6%. Although ventricular tachycardia/fibrillation (VT/VF) constitutes only 30-35% of all cardiac arrests, more than 80% of survivors present with VT/VF. These patients are also likely to have an underlying reversible cause. Patients with refractory VT/VF, who have been emergently transported to the cardiac catheterization laboratory (CCL) with CPR in progress, have been shown to have a >80% incidence of clinically significant coronary stenosis. Thus, VT/VF is a strong predictor of acute coronary occlusion or stenosis, potentially amenable to timely percutaneous coronary intervention (PCI). The refractory VT/VF population with the worst prognosis (15% death rate) has the highest incidence of a treatable underlying cause. This subgroup offers the greatest opportunity to impact OHCA survival and public health. Advanced perfusion/reperfusion strategies now make it feasible to potentially reverse the underlying cause, including mechanical CPR, and extracorporeal membrane oxygenation (ECMO) before and/or after PCI. Thus, investigators submitting this application implemented a Refractory VT/VF Protocol as a standard of care in Minneapolis/St. Paul through the comprehensively integrated, and collaborative Minnesota Resuscitation Consortium (MRC). During the first 12 months of protocol implementation, 62 sequential patients entered the CCL with CPR in progress. Overall, survival to hospital discharge occurred in 28(45%) and functionally favorable survival (Cerebral Performance Category 1 or 2) occurred in 26 (42%). Of the survivors, 26/28 (90%) had CPC 1 at one month. Historical and concurrent data for the same population receiving standard resuscitation practice in MSP show survival of 15% with CPC 1 OR 2. Proposed Clinical Trial We propose a single center, prospective feasibility/efficacy clinical trial, to assess the role of early ECMO-facilitated CCL access compared to ED based resuscitation when ROSC is required for CCL access. Both strategies represent current standards of care in our community. Two EMS systems transport patients to the ED where resuscitation is continued until ROSC, followed by CCL access, or death is declared. Three EMS systems transport patients to the University of MN for the ECMO-based early CCL access protocol. Our 18-month preliminary experience shows that ECMO-based early CCL patients have higher functionally favorable survival rates than conventional resuscitation practice. Specific Aim. Compare the rates of survival to hospital discharge with Modified Rankin Scale Score (mRS) ?3 in adult patients (18-75 years old) with refractory VT/VF OHCA that are mobilized early to the U of MN and randomized to receive either: 1) continued ED based resuscitation until achievement of ROSC followed by CCL access and PCI or determination of death, or 2) early CCL access for ECMO support and PCI when needed. Assess the cost associated with such a strategy. Significance. If our study results indicate potential efficacy, it will provide the basis for a future multicenter clinical trial to assess definitive survival benefit and generalizability of this approach.